Wiskott-Aldrich syndrome

BACKGROUND

Wiskott-Aldrich syndrome (WAS) is an inherited, immunodeficiency disorder that occurs almost exclusively in males. The recessive genetic disorder is caused by a mutation in the WAS (Wiskott-Aldrich syndrome) gene, which is an X-linked trait. The gene mutation leads to abnormalities in B- and T-lymphocytes (white blood cells), as well as blood platelet cells. In a healthy individual, the T-cells provide protection against viral and fungal infection, the B cells produce antibodies, and platelets are responsible for blood clotting to prevent blood loss after a blood vessel injury.

Individuals diagnosed with WAS suffer from recurrent infections, eczema and thrombocytopenia (low levels of platelets).

Before 1935, patients only lived an average of eight months. Today, patients usually live an average of eight years, according to a recent case study. The cause of death is usually attributed to extensive blood loss. However, cancer (especially leukemia) is common and often fatal among WAS patients.

The only possible cure for WAS is a bone marrow transplant. However, if a patient's family member is not a possible match for a bone marrow donation, patients may have to wait years for a potential donor. Other aggressive treatments may also increase a patient's life expectancy. For instance, one study found that patients who underwent splenectomy (removal of the spleen) lived to be more than 25 years old. The spleen may harbor too many platelets, and cause a decrease in the number of platelets in circulation. Antibiotics, antivirals, antifungals, chemotherapeutic agents, immunoglobulins and corticosteroids have also been used to relieve symptoms and treat infections and cancer associated with WAS.

Researchers estimate that about four people per one million live male births develop the disease in the United States.

The syndrome is named after Dr. Robert Anderson Aldrich, an American pediatrician who described the disease in a family of Dutch-Americans in 1954, and Dr Alfred Wiskott, a German pediatrician who discovered the syndrome in 1937. Wiskott described three brothers with a similar disease, whose sisters were unaffected.

CAUSES

Individuals who have the disease have a mutated WAS (Wiskott-Aldrich syndrome) gene, which codes for the protein named Wiskott-Aldrich Syndrome Protein (WASP). This protein is present in leukocytes (white blood cells that fight against infection), as well as platelets. Consequently, individuals who are diagnosed with WAS are more susceptible to infections and bleeding.

The disease is inherited as an X-linked recessive trait. Therefore, it affects males almost exclusively. If a male inherits the mutated WAS gene, he will develop the disease because he has only one X chromosome.

Females, on the other hand, have two X chromosomes. Even if a female inherits the mutated gene, chances are the other gene will be healthy because the disease is extremely rare. The female would need to inherit two mutated X chromosomes in order to develop the disease. However, if the female inherits one mutated gene she is a carrier for the disease, and there is a 50% chance she will pass the gene to each of her children. Carriers do not express symptoms of the disease.

SYMPTOMS

WAS symptoms range from mild to severe and begin early in childhood. A less severe form of the disease will mainly affect the platelets. Common symptoms include eczema, thrombocytopenia, immune deficiency and bloody diarrhea.

Individuals who have WAS are more susceptible to bleeding and infections, as well as malignancies like lymphoma or leukemia. Common infections include otitis media (ear infections), sinusitis, pneumonia, herpes simplex and the Epstein-Barr virus (EBV). In addition, WAS patients frequently suffer from autoimmune disorders like vasculitis (inflamed blood vessels), arthritis and autoimmune hemolytic anemia.

About 81% of individuals with WAS develop eczema, a skin disorder that causes red itchy patches of skin on the face, elbows, knees and arms. Eczema usually improves as the patient ages. However, in some cases, persistent eczema and skin rashes may cause secondary infections. Other complications may include cellulitis (inflamed connective tissue), abscesses or erythroderma (reddening of the skin).

DIAGNOSIS

WAS is diagnosed when the mutated gene is identified. Some individuals may experience physical symptoms and a blood test may detect thrombocytopenia. Gene testing is also available for possible carriers of the disease and for fetuses.

Amniocentesis: Amniocentesis may be performed to detect genetic abnormalities in the fetus. This procedure is performed at about 15-18 weeks gestation. During the procedure a long, thin needle is inserted into the pregnant woman's abdominal wall to the uterus. A small amount of fluid is removed from the sac surrounding the fetus. The fluid is then analyzed for genetic abnormalities. There is a slight risk of infection or injury to the fetus, and a chance of miscarriage.

CBC: A complete blood count (CBC) test is usually conducted to determine how many and what types of cells are in the blood. Patients who have WAS will have a low platelet count and weak immune response. Healthy individuals have anywhere from 150,000 to 450,000 platelets per microliter of circulating blood in the body. The risk of bleeding increases as the number of platelets decreases. When there are less than 10,000 platelets per microliter of circulating blood, the condition is considered severe, and internal bleeding may occur.

Chorionic villus sampling: During chronionic villus sampling (CVS), a small piece of tissue (chorionic villi) is removed from the uterus during early pregnancy to screen the fetus for genetic defects. Depending on where the placenta is located, CVS can be performed through the cervix (transcervical) or through the abdomen (transabdominal). The risks of infections or fetal damage are slightly higher than the risks of amniocentesis. Fetal loss occurs about two percent of the time.

DNA test: The DNA from a sample of blood can be analyzed for a mutation in the WAS gene. This test can confirm a diagnosis and will also help the healthcare provider predict how severe the form of the disease will be. In addition, if the specific WAS gene mutation is identified in an affected child, that child's mother can be tested to confirm that she is a carrier.

TREATMENT

Currently, the only known cure for the disease is a bone marrow transplant. A splenectomy may increase the patient's life expectancy. Also, antibiotics, antivirals, antifungals, chemotherapeutic agents, immunoglobulins and corticosteroids are used to relieve symptoms and treat infections associated with WAS.

Antibiotics: Antibiotics have been used to treat bacterial infections and for prophylaxis in patients who have had a splenectomy.

Antifungals: Antifungal agents are used to treat patients who experience fungal infections associated with WAS.

Antivirals: Some patients are given antiviral medicines like Valacyclovir (Valtrex©) or Famciclovir (Famvir©) to treat herpes simplex.

Bone marrow transplant: Currently, the only known cure for WAS is a bone marrow transplant. The healthy bone marrow must match the patient's tissue type. It can be taken from the patient, a living relative (usually a sibling) or from an unrelated donor (found through the national marrow donor program). Donors are matched through special blood tests called HLA (human leukocyte antigens) tissue typing.

Chemotherapy agents: Chemotherapy agents are used to treat lymphoreticular and/or hematological malignancy. Chemotherapy agents like busulfan are also used as ablative agents (with or without irradiation) before bone marrow transplantation.

Corticosteroids: Corticosteroids like Prednisone (Deltasone©, Orasone© or Sterapred©) have been used to decrease inflammation associated with WAS. Treatment generally lasts two to three weeks.

Immune Globulin Intravenous Injection (IGIV): IGIV injections like Gamimune N©, Gammagard S/D© or Sandoglobulin© have been administered to boost the body's immune response and decrease the risk of infections. During the procedure blood products containing immunoglobulins are injected into the bloodstream. The process also increases the number of platelets in the blood, reducing symptoms of thrombocytopenia. Treatment usually lasts from two weeks to three months.

Splenectomy: Some patients may have their spleen surgically removed (splenectomy) to increase the level of platelets in the blood.

Topical steroids: Topical corticosteroids (like hydrocortisone, betamethasone or fluticasone propionate) are the most common and effective treatments for eczema, which is a common symptom of WAS. These medications are used until the rash clears up. Low-strength topical corticosteroids should be used on the face. Over-the-counter hydrocortisone (like Bactine©, Cortaid©, Dermolate© or Aveeno Anti-Itch cream©) is a low-strength corticosteroid cream that has been used to treat young children.

INTEGRATIVE THERAPIES

Note : Currently, there is a lack of scientific data on the use of integrative therapies for the treatment or prevention of Wiskott-Aldrich syndrome (WAS). The integrative therapies listed below should be used only under the supervision of a qualified healthcare provider, and should not be used in replacement of other proven therapies or preventive measures.

Strong scientific evidence :

Probiotics : Probiotics are beneficial bacteria and are sometimes called friendly germs. They help maintain a healthy intestine by keeping harmful bacteria and yeasts in the gut under control. Most probiotics come from food sources, especially cultured milk products. Probiotics can be taken as capsules, tablets, beverages, powders, yogurts, and other foods. An increasing number of studies support the use of probiotics as a supplement to antibiotic therapy. Probiotic supplementation during a course of antibiotics has been studied for reducing adverse effects of antibiotics in the intestinal environment. This includes reducing growth of Clostridium difficile bacteria, which can lead to colitis, a common complication of antibiotics, especially in the elderly. Some probiotics may also help prevent the development of antibiotic resistance. In acutely ill children, synbiotics have been linked to greater weight gain and fewer bacterial illnesses after antibiotics are ended. The evidence consistently supports supplementation of antibiotics with probiotics.

Probiotics are generally considered to be safe and well-tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant. Caution is advised when using probiotics in neonates born prematurely or with immune deficiency.

Good scientific evidence :

Ginseng : For more than 2,000 years, the roots of ginseng have been valued in Chinese medicine. Several studies suggest that ginseng may be an effective agent for immune system enhancement. Additional high quality research is needed before a conclusion be made.

Avoid with known allergy to plants in the Araliaceae family. There has been a report of a serious life-threatening skin reaction, possibly caused by contaminants in ginseng formulations.

Probiotics : Research suggests that probiotics, especially those in milk or food, may be an effective agent for immune system enhancement. However, commercially produced yogurt may not be as effective. More studies are needed, particularly with yogurt, to give recommendations.

Probiotics are generally considered safe and well-tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant. Caution is advised when using probiotics in neonates born prematurely or with immune deficiency.

Zinc : Zinc formulations have been used since ancient Egyptian times to enhance wound healing. Zinc appears to be an essential trace element for the immune system, but research on the effect of zinc supplementation on immune function is scant and mostly focuses on patients with specific diseases. Zinc gluconate appears to exert beneficial effects on immune cells, improving CD3 and CD4 counts and increasing CD4/CD8 ratios in children. There are relatively few studies that examine zinc levels and the effects of zinc supplementation on the health of the elderly population. Further research is needed before a recommendation can be made.

Zinc is generally considered safe when taken at the recommended dosages. Avoid zinc chloride since studies have not been done on its safety or effectiveness. Avoid with kidney disease. Use cautiously if pregnant or breastfeeding.

Unclear or conflicting scientific evidence :

Amaranth oil : Amaranth is grown in Asia and the Americas and harvested primarily for its grain, which is used as a food source for bread, pasta, and infant food. Limited evidence suggests that amaranth may stimulate the immune system when combined with a heart-healthy diet in patients with heart disease and high cholesterol. However, additional studies of amaranth alone are needed to determine if it is effective for immunomodulation.

Amaranth is generally considered safe. Avoid if allergic or sensitive to amaranth. Use cautiously with diabetes, low blood sugar, low blood pressure, immune system disorders, or kidney disorders. Use cautiously if pregnant or breastfeeding.

Arabinogalactan : Arabinogalactans belong to a group of carbohydrates called polysaccharides. When consumed in the diet, arabinogalactan comes from the wood of the larch tree (Larix species) and is approved for use as a dietary fiber by the U.S. Food and Drug Administration (FDA). Early research has suggested that arabinogalactan may cause immune stimulation; however, its effect on immunity in healthy volunteers is not clear. More evidence is needed.

Avoid if allergic or sensitive to arabinogalactan or larch. People who are exposed to arabinogalactan or larch dust may have irritation of the eyes, lungs, or skin. Use cautiously in people with diabetes, digestive problems, or immune system disorders, and in people who consume diets high in fiber or low in galactose. Arabinogalactan should not be used during pregnancy or breastfeeding.

Arginine (L-arginine) : L-arginine helps maintain the body's fluid balance (urea, creatinine), and aids in wound healing, hair growth, sperm production (spermatogenesis), blood vessel relaxation (vasodilation), and fights infection. Preliminary study results suggest that arginine may cause immunomodulation. More studies are needed to confirm these results.

Avoid if allergic to arginine or with a history of stroke or liver or kidney disease. Avoid if pregnant or breastfeeding. Use cautiously if taking blood-thinning drugs (like warfarin or Coumadin©) or blood pressure drugs or herbs or supplements with similar effects. Blood potassium levels should be monitored. L-arginine may worsen symptoms of sickle cell disease. Caution is advised in patients taking prescription drugs to control sugar levels.

Astragalus : In traditional Chinese medicine (TCM), astragalus is commonly found in mixtures with other herbs. Western herbalists began using astragalus in the 1800s as an ingredient in various tonics. Astragalus has been suggested as an immune system stimulant in preliminary laboratory and animal research, and in traditional accounts. Reliable human studies are lacking. High quality human research is necessary before a firm conclusion can be drawn.

Avoid if allergic to astragalus, peas, or any related plants or with a history of Quillaja bark-induced asthma. Avoid with aspirin or aspirin products or herbs or supplements with similar effects. Avoid with inflammation or fever, stroke, transplant, or autoimmune diseases. Stop use two weeks before and immediately after surgery/dental/diagnostic procedures with a risk of bleeding. Use cautiously with bleeding disorders, diabetes, high blood pressure, lipid disorders, or kidney disorders. Use cautiously with blood-thinners, blood sugar drugs, or diuretics or herbs and supplements with similar effects. Avoid if pregnant or breastfeeding.

Beta-carotene : Beta-carotene is a member of the carotenoids, which are very colorful (red, orange, yellow), fat-soluble compounds. They are naturally found in many fruits, grains, oil, and vegetables, including green plants, carrots, sweet potatoes, squash, spinach, apricots, and green peppers. Preliminary research of beta-carotene for immune system enhancement shows mixed results. Further research is needed before a conclusion can be drawn.

Avoid if sensitive to beta-carotene, vitamin A or any other ingredients in beta-carotene products.

Berberine : In low-quality research, berberine has been shown to significantly increase platelet production in individuals with thrombocytopenia both as a monotherapy and adjunctive therapy.

Avoid if allergic to berberine, to plants that contain berberine (Hydrastis canadensis (goldenseal), Coptis chinensis (coptis or goldenthread), Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), and Berberis aristata (tree turmeric)), or to members of the Berberidaceae family. Berberine has been reported to cause nausea, vomiting, hypertension (high blood pressure), respiratory failure, and paresthesias; however, clinical evidence of such adverse effects is not prominent in the literature. Avoid if pregnant or breastfeeding.

Black currant : The black currant shrub is native to Europe and parts of Asia and is particularly popular in Eastern Europe and Russia. There is currently a lack of information in humans on the effectiveness of black currant seed for immunomodulation.

Avoid if allergic or hypersensitive to black currant, its constituents, or plants in the Saxifragaceae family. Avoid with hemophilia or in those taking blood thinners, unless otherwise recommended by a qualified healthcare provider. Use cautiously with venous disorders or gastrointestinal disorders. Use cautiously if taking MAOIs (antidepressants) or vitamin C supplements. Avoid if pregnant or breastfeeding.

Bovine colostrum : Bovine colostrum is the pre-milk fluid produced from cow mammary glands during the first two to four days after birth. Bovine colostrum confers growth, nutrient, and immune factors to the offspring. Bovine colostrum contains immunoglobulins or antibodies that are released into the bloodstream in response to infections. These immunoglobulins may help improve immune function and may be effective in treating immune system deficiencies. More evidence is required before a firm conclusion can be made.

Avoid if allergic or hypersensitive to dairy products. Use bovine colostrum with caution. Toxic compounds, such as polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), and dichlordiphenyldichloroethylene (DDE) have been found in human colostrum and breast milk. Thus, it is possible that these agents may be found in bovine colostrum. Avoid with, or if at risk of developing, cancer. Use cautiously with immune system disorders, atherosclerosis (hardening of the arteries) or if taking medications, such as anti-diarrheal agents (e.g. immodium), insulin, or CNS agents (amphetamines, caffeine). Avoid if pregnant or breastfeeding.

Cat's claw : Cat's claw is widely used in the United States and Europe, and it is one of the top herbal remedies sold despite a lack of high-quality human evidence. Preliminary research of cat's claw for immune system enhancement shows mixed results. Further research is needed before a conclusion can be drawn.

Avoid if allergic to Cat's claw or Uncaria plants or plants in the Rubiaceae family such as gardenia, coffee, or quinine. Avoid with a history of conditions affecting the immune system (such as AIDS, HIV, some types of cancer, multiple sclerosis, tuberculosis, rheumatoid arthritis, or lupus). Use cautiously with bleeding disorders or history of stroke, or if taking drugs that may increase the risk of bleeding. Stop use two weeks before and immediately after surgery/dental/diagnostic procedures with bleeding risks. Cat's claw may be contaminated with other Uncaria species. Reports exist of a potentially toxic, Texan grown plant, Acacia gregii being substituted for cat's claw. Avoid if pregnant, breastfeeding, or trying to become pregnant.

Copper : Copper is a mineral that occurs naturally in many foods, including vegetables, legumes, nuts, grains, fruits, shellfish, avocado, beef, and animal organs, (e.g. liver and kidney). Copper is involved in the development of immune cells and immune function in the body. Severe copper deficiency appears to have adverse effects on immune function, although the exact mechanism is not clear.

Avoid if allergic/hypersensitive to copper. Avoid use of copper supplements during the early phase of recovery from diarrhea. Avoid with hypercupremia, occasionally observed in disease states, including cutaneous leishmaniasis, sickle-cell disease, unipolar depression, breast cancer, epilepsy, measles, Down syndrome, and controlled fibrocalculous pancreatic diabetes (a unique form of secondary diabetes mellitus). Avoid with genetic disorders affecting copper metabolism such as Wilson's disease, Indian childhood cirrhosis, or idiopathic copper toxicosis. Avoid with HIV/AIDS. Use cautiously with water containing copper concentrations greater than 6mg/L. Use cautiously with anemia, arthralgias, or myalgias. Use cautiously if taking oral contraceptives. Use cautiously if at risk for selenium deficiency. The U.S. Recommended Dietary Allowance (RDA) is 1,000 micrograms for pregnant women. The U.S. RDA is 1,300 micrograms for nursing women.

Dong quai : Poor-quality research reports benefits of Dong quai in patients diagnosed with idiopathic thrombocytopenic purpura (ITP). However, these patients were not compared to individuals who were not receiving Dong quai. Therefore, the results can only be considered preliminary.

Avoid if allergic to Angelica radix or members of the Aplaceae/Umbelliferae family (anise, caraway, carrot, celery, dill, parsley). Although Dong quai is accepted as being safe as a food additive in the United States and Europe, its safety in medicinal doses is not known. There are no reliable long-term studies of side effects. Most precautions are based on theory, laboratory research, tradition, or isolated case reports. Avoid if pregnant or breastfeeding.

Echinacea : Echinacea is a perennial herb that has been used to treat a variety of medical conditions. Echinacea has been studied alone and in combination preparations for immune system stimulation. It remains unclear if there are clinically significant benefits. Additional studies are needed in this area before conclusions can be drawn regarding safety or effectiveness.

Avoid if allergic to echinacea, its constituents, or any members of the Asteraceae/Compositae family (ragweed, chrysanthemums, marigolds, daisies). Use cautiously in patients prone to atopic reactions and in those with hemochromatosis and diabetes. Some natural medicine experts discourage the use of echinacea by people with conditions affecting the immune system, such as HIV/AIDS, some types of cancer, multiple sclerosis, tuberculosis, and rheumatologic diseases (such as rheumatoid arthritis or lupus). Use parenteral preparations of echinacea (no longer approved for use in Germany) cautiously. Use tinctures cautiously with alcoholic patients or in patients taking disulfiram or metronidazole. Avoid using echinacea in patients presenting for anesthesia. Use cautiously if pregnant or breastfeeding.

Gamma linolenic acid (GLA) :Gamma linolenic acid (GLA) is a dietary fatty acid that is found in many plant oil extracts. Few clinical trials have investigated the effect of GLA on immune responses in healthy human subjects. GLA, as blackcurrant seed oil, may offer some benefits. Further study is required to determine if GLA is beneficial for immune enhancement.

Use cautiously with drugs that increase the risk of bleeding like anticoagulants and anti-platelet drugs. Avoid if pregnant or breastfeeding.

Goldenseal : Goldenseal is one of the five top-selling herbal products in the United States. Goldenseal is sometimes suggested to be an immune system stimulant. However, there is little clinical evidence in this area. More research is needed before a firm conclusion can be drawn.

Avoid if allergic or hypersensitive to goldenseal or any of its constituents (like berberine and hydrastine). Use cautiously with bleeding disorders, diabetes, or low blood sugar levels. Avoid if pregnant or breastfeeding.

Licorice : Early study has suggested that recombinant roasted licorice decoction combined with low-dose glucocorticoids may be more effective than glucocorticoids alone in treating idiopathic thrombocytopenic purpura. This combination has also shown a lower adverse effect rate than glucocorticoids alone.

Avoid with a known allergy to licorice, any component of licorice, or any member of the Fabaceae (Leguminosae) plant family. Avoid with congestive heart failure, coronary heart disease, kidney or liver disease, fluid retention, high blood pressure, hormonal abnormalities or with diuretics. Licorice can cause abnormally low testosterone levels in men or high prolactin or estrogen levels in women. This may make it difficult to become pregnant and may cause menstrual abnormalities.

Maitake mushroom : Maitake mushrooms (Grifola frondosa) are fungi that can be eaten. Maitake has been used both as a food and for medical conditions. Beta-glucan extracts from maitake have been studied for immune stimulation. Additional high quality research is needed to make a conclusion.

Maitake has not been studied thoroughly in humans, and its effects are not well known. Because it has been used historically as a food, it is thought that low doses may be safe. Avoid if allergic or hypersensitive to maitake or its constituents. Use cautiously with low blood pressure, diabetes, or low blood sugar. Use cautiously if taking blood pressure medications, antidiabetic agents, immunostimulants, immunosuppressants, or interferons. Avoid if pregnant or breastfeeding.

Massage : The main goal of massage is to help the body heal itself. Touch is fundamental to massage therapy and is used by therapists to locate painful or tense areas, to determine how much pressure to apply, and to establish a therapeutic relationship with clients. Preliminary evidence suggests that massage therapy may preserve immune function. Further research is needed before a firm conclusion can be made.

Avoid with bleeding disorders, low platelet counts, or if taking blood-thinning medications (such as heparin or warfarin/Coumadin©). Areas should not be massaged where there are fractures, weakened bones from osteoporosis or cancer, open/healing skin wounds, skin infections, recent surgery, or blood clots. Use cautiously with a history of physical abuse or if pregnant or breastfeeding. Massage should not be used as a substitute for more proven therapies for medical conditions. Massage should not cause pain to the client.

Meditation : Many forms of meditation have been practiced for thousands of years throughout the world, with many techniques originating in Eastern religious practices. Preliminary research reports increased antibody response after meditation. Further study is needed to better determine if meditation affects immune function.

Use cautiously with underlying mental illnesses. People with psychiatric disorders should consult with their primary mental healthcare professionals before starting meditation and should explore how meditation may or may not fit in with their current treatment plans. Avoid with risk of seizures. The practice of meditation should not delay the time to diagnosis or treatment with more proven techniques or therapies, and should not be used as the sole approach to illnesses.

Melatonin : Increased platelet counts after melatonin use has been observed in patients with decreased platelets due to cancer therapies (several studies reported by the same author). Stimulation of platelet production has been suggested but not clearly demonstrated. Additional research is necessary to better understand the role of melatonin in thrombocytopenia.

There are rare reports of allergic skin reactions after taking melatonin by mouth. Melatonin has been linked to a case of autoimmune hepatitis. Based on available studies and clinical use, melatonin is generally regarded as safe in recommended doses for short-term use. Melatonin supplementation should be avoided in women who are pregnant or attempting to become pregnant, based on possible hormonal effects. High levels of melatonin during pregnancy may increase the risk of developmental disorders. In animal studies, melatonin is detected in breast milk and therefore should be avoided during breastfeeding. In men, decreased sperm motility and decreased sperm count are reported with use of melatonin.

Mistletoe : Once considered a sacred herb in Celtic tradition, mistletoe has been used for centuries for high blood pressure, epilepsy, exhaustion, anxiety, arthritis, vertigo (dizziness), and degenerative inflammation of the joints. A few small trials found mistletoe to be promising as an immunostimulant in individuals with the common cold. Further study is needed to determine if mistletoe is effective for immunomodulation.

Avoid if allergic or hypersensitive to mistletoe or to any of its constituents. Anaphylactic reactions (life threatening shock) have been described after injections of mistletoe. Avoid with acute, highly febrile, inflammatory disease, thyroid disorders, seizure disorders, or heart disease. Use cautiously with diabetes, glaucoma, or if taking cholinergics.

Qi gong : Qi gong is a type of traditional Chinese medicine (TCM) that is thought to be at least 4,000 years old. It is traditionally used for spiritual enlightenment, medical care, and self-defense. There is some evidence suggesting that internal Qi gong may help with treatment of immune deficiencies. However, the evidence is still unclear, and further research is needed to understand how Qi gong may potentially benefit immune function. Based on preliminary study, Chan-Chuang Qi gong therapy may be used to treat leukopenia (low white blood cell count) in breast cancer patients treated with chemotherapy. Further study is warranted.

Qi gong is generally considered to be safe in most people when learned from a qualified instructor. Use cautiously with psychiatric disorders.

Probiotics : Results are mixed regarding the ability of probiotics to reduce complications of infections from medical treatment. Reduced incidence of infection has been seen in patients treated for brain injury, abdominal surgery, and liver transplantation. Other studies have shown no such reduction in elective abdominal surgery and critical care patients.More research is needed in this area before a conclusion can be drawn.

Probiotics are generally considered safe and well-tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant. Caution is advised when using probiotics in neonates born prematurely or with immune deficiency.

Reflexology : Reflexology involves the application of manual pressure to specific points or areas of the feet called "reflex points" that are believed to correspond to other parts of the body. Some research suggests that self-administered reflexology may be beneficial for immune enhancement. Additional study is needed in this area.

Avoid with recent or healing foot fractures, unhealed wounds, or active gout flares affecting the foot. Use cautiously and seek prior medical consultation with osteoarthritis affecting the foot or ankle or with severe vascular disease of the legs or feet. Use cautiously with diabetes, heart disease, unstable blood pressure, cancer, active infections, past episodes of fainting (syncope), mental illness, gallstones, kidney stones, or with a pacemaker. Use cautiously if pregnant or breastfeeding. Reflexology should not delay diagnosis or treatment with more proven techniques or therapies.

Rose hip : Rose hips are the fruits that develop from the blossoms of the wild rose plant. It is unclear if rose hips affect immune function. More studies are needed in this area.

Avoid if allergic to rose hips, rose pollen, their constituents, or members of the Rosaceae family. Use cautiously if taking anticoagulant or anti-platelet aggregating agents, anticancer agents, anti-HIV medications, anti-inflammatory agents, antilipemics, aluminum-containing antacids, antibiotics, salicylates or salicylate-containing herbs, or laxatives. Use cautiously in patients who are avoiding immune system stimulants.

Shiitake : Lentinan, a constituent of shiitake, has been shown to modulate the immune system in some studies. However, there is currently a lack of reliable human evidence supporting the use of lentinan or shiitake for immunomodulation. Additional study is needed in this area.

Avoid if allergic or hypersensitive to shiitake mushrooms. Avoid if pregnant or breastfeeding.

Tai chi : Tai chi is a system of movements and positions believed to have developed in 12th Century China. Tai chi techniques aim to address the body and mind as an interconnected system and are traditionally believed to have mental and physical health benefits to improve posture, balance, flexibility, and strength. Tai chi may increase the body's immune response in older adults. For example, patients receiving varicella vaccines and who practiced tai chi showed increased immune responses. Although early study is promising, more study is needed to better determine if tai chi is effective for immune system stimulation.

Avoid with severe osteoporosis or joint problems, acute back pain, sprains, or fractures. Avoid during active infections, right after a meal, or when very tired. Some believe that visualization of energy flow below the waist during menstruation may increase menstrual bleeding. Straining downwards or holding low postures should be avoided during pregnancy, and by people with inguinal hernias. Some tai chi practitioners believe that practicing for too long or using too much intention may direct the flow of chi (qi) inappropriately, possibly resulting in physical or emotional illness. Tai chi should not be used as a substitute for more proven therapies for potentially serious conditions. Advancing too quickly while studying tai chi may increase the risk of injury.

Thymus extract : Thymus extracts for nutritional supplements are usually derived from young calves (bovine). Preliminary evidence suggests that thymus extract increases white blood cell counts. Additional study is needed to determine if thymus extract is effective for immune system stimulation.

Avoid if allergic or hypersensitive to thymus extracts. Use bovine thymus extract supplements cautiously due to the potential for exposure to the virus that causes "mad cow disease." Avoid use with an organ transplant or other forms of allografts or xenografts. Avoid with thymic tumors, myasthenia gravis (neuromuscular disorder), or untreated hypothyroidism. Avoid if taking hormonal therapy or immunosuppressants. Avoid if pregnant or breastfeeding; thymic extract increases human sperm motility and progression.

Vitamin A : Vitamin A is a fat-soluble vitamin. Vitamin A deficiency may compromise immunity, but there is no clear evidence that additional vitamin A supplementation is beneficial for immune function in patients who are not vitamin A deficient.

Avoid if allergic or hypersensitive to vitamin A. Vitamin A toxicity may occur if taken at high dosages. Use cautiously with liver disease or alcoholism. Smokers who consume alcohol and beta-carotene may be at an increased risk for lung cancer or heart disease. Vitamin A appears safe in pregnant women if taken at recommended doses; however, vitamin A excess, as well as deficiency, has been associated with birth defects. Use cautiously if breastfeeding because the benefits or dangers to nursing infants are not clearly established.

Vitamin B6 : Major sources of vitamin B6 include: cereal grains, legumes (beans), vegetables (like carrots, spinach, peas), potatoes, milk, cheese, eggs, fish, liver, meat, and flour. Vitamin B6 has been shown to be important for immune system function in older individuals. One study found that the amount of vitamin B6 required to reverse immune system impairments in elderly people was more than the current recommended dietary allowance (RDA). Well-designed clinical trials on vitamin B6 supplementation for this indication are needed before a conclusion can be made.

Vitamin B6 is likely safe when used orally in doses not exceeding the recommended dietary allowance (RDA). Avoid if sensitive or allergic to any vitamin B6 product ingredients. Some individuals seem to be particularly sensitive to vitamin B6 and may have problems at lower doses. Avoid excessive dosing. Use cautiously if pregnant or breastfeeding.

Vitamin D : Vitamin D is found in many foods, including fish, eggs, fortified milk, and cod liver oil. The sun also helps the body produce vitamin D. Preliminary human evidence suggests that vitamin D and its analogues, such as alfacalcidol, may act as immunomodulatory agents. High quality clinical studies are needed to better understand the effects of vitamin D on immunomodulation.

Avoid if allergic or hypersensitive to vitamin D or any of its components. Vitamin D is generally well-tolerated in recommended doses; doses higher than recommended may cause toxic effects. Use cautiously with hyperparathyroidism (overactive thyroid), kidney disease, sarcoidosis, tuberculosis, and histoplasmosis. Vitamin D is safe in pregnant and breastfeeding women when taken in recommended doses.

Vitamin E : Vitamin E exists in eight different forms ("isomers"): alpha, beta, gamma and delta tocopherol; and alpha, beta, gamma, and delta tocotrienol. Alpha-tocopherol is the most active form in humans. Studies of the effects of vitamin E supplementation on immune system function have yielded mixed results. Further research is needed before a clear conclusion can be drawn.

Avoid if allergic or hypersensitive to vitamin E. Avoid with retinitis pigmentosa (loss of peripheral vision). Use cautiously with bleeding disorders or if taking blood thinners. Avoid doses greater than the recommended daily level in pregnant women and breastfeeding women.

Fair negative scientific evidence :

DHEA : DHEA (dehydroepiandrosterone) is a hormone that is produced by the adrenal glands. It is suggested by some textbooks and review articles that DHEA may be effective for immune system stimulation. However, current scientific evidence does not support this claim.

Avoid if allergic to DHEA. Avoid with a history of seizures. Use cautiously with adrenal or thyroid disorders or if taking anticoagulants or drugs, herbs, or supplements for diabetes, heart disease, seizure, or stroke. Stop use two weeks before and immediately after surgery/dental/diagnostic procedures with bleeding risks. Avoid if pregnant or breastfeeding.

Lycopene : Lycopene is a carotenoid found in human serum, and skin, liver, adrenal, lung, prostate, and colon tissue. It has been proposed that lycopene and other carotenoids, such as beta-carotene, may stimulate the immune system. However, several studies of lycopene supplements and tomato juice intake in humans do not report effectiveness for immune stimulation.

Avoid if allergic to tomatoes or to lycopene. Due to a lack of conclusive data, avoid if pregnant or breastfeeding

PREVENTION

There is currently no known method to prevent WAS. However, individuals can be tested to determine whether they are carriers of the disease.

AUTHOR INFORMATION

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

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• Jin Y, Mazza C, Christie JR, et al. Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation. Blood. 2004 Dec 15;104(13):4010-9. Epub 2004 Jul 29. View abstract
• Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com. Copyright © 2009. Accessed May 25, 2009.
• St. Jude Children's Research Hospital. Inherited Immunodeficiencies: Wiskott-Aldrich Syndrome (WAS). www.stjude.org. Accessed May 25, 2009.
• U.S. Immune Deficiency Foundation. The Wiskott Aldrich Syndrome. www.primaryimmune.org. Accessed May 25, 2009.